Aniek Lamberts

Significantly higher prevalence of circulating bullous pemphigoid-specific IgG autoantibodies in elderly patients with a nonbullous skin disorder

DEAR EDITOR, We read with interest the recent article of van Beek et al. on ‘Serum autoantibodies against the dermal– epidermal junction in patients with chronic pruritic disorders, elderly individuals and blood donors prospectively recruited’ and the recent review article of Schmidt et al. on ‘BP180and BP230-specific IgG autoantibodies in pruritic disorders of the elderly: a preclinical stage of bullous pemphigoid?’ about the association between pruritus in the elderly and the presence of bullous pemphigoid (BP)-specific IgG autoantibodies. van Beek et al. studied autoantibody reactivity against the epidermal basement membrane zone (EBMZ) by indirect immunofluorescence (IIF) microscopy, enzyme-linked immunosorbent assay (ELISA) and immunoblot. Positive reactivity in any test was found in 31% of the sera of elderly individuals (≥ 70 years; n = 93), 17% of the sera of patients with chronic pruritic disorders (n = 78) and 26% of the sera of healthy blood donors of all ages (n = 50). In our opinion these are remarkably high percentages, probably due to the false-positive rates of the immunoassays, as mentioned in the discussion of their article. van Beek et al. concluded that neither advanced age nor chronic pruritus have been verified as risk factors for autoantibodies against the EBMZ. Schmidt et al. reviewed clinical and experimental studies about the possible association between senile pruritus and BP IgG autoantibodies, and questioned whether this could be a preclinical stage of BP. Prior studies by Rieckhoff-Cantoni et al., Hofmann et al. and Feliciani et al. on the presence of circulating BP autoantibodies in elderly patients with pruritic disorders, but without blistering, reported IgG reactivity against BP180 or BP230 in 10 of 43 patients (23%), three of 25 patients (12%) and five of 15 patients (33%), respectively. The question remains whether circulating autoantibodies against BP antigens in the elderly and patients with pruritic disorders indicate the presence of a BP subtype, may identify patients with an increased risk of developing BP, or may have no clinical relevance at all. As an extension to these studies we present our results of a retrospective database study, which included 374 patients who consulted our department for a skin disorder, without blistering. Data were collected from patients in our dermatology database in whom direct immunofluorescence (DIF) and serological testing were performed at the University Medical Center Groningen. Patients were excluded if DIF was positive or if they presented clinically with blisters or erosions on skin or mucous membranes, to exclude those with an evident diagnosis of an autoimmune blistering disease. The patient characteristics are shown in Table 1. The following serological test results were studied: IIF on monkey oesophagus, IIF on salt-split skin, immunoblot testing on BP180 and BP230 antibodies, and BP180 NC16Aand BP230-specific ELISAs (MBL, Nagoya, Japan; cut-off < 9 U mL ) (Fig. 1).

Effectiveness and Safety of Rituximab in Recalcitrant Pemphigoid Diseases

Introduction Rituximab (RTX) is a monoclonal antibody targeting CD20, a transmembrane protein expressed on B cells, causing B cell depletion. RTX has shown great efficacy in studies of pemphigus vulgaris, but data of pemphigoid diseases are limited. Objective To assess the effectiveness and safety of RTX in pemphigoid diseases. Methods The medical records of 28 patients with pemphigoid diseases that were treated with RTX were reviewed retrospectively. Early and late endpoints, defined according to international consensus, were disease control (DC), partial remission (PR), complete remission (CR), and relapses. Safety was measured by reported adverse events. Results Patients with bullous pemphigoid (nu2009=u20098), mucous membrane pemphigoid (nu2009=u200914), epidermolysis bullosa acquisita (nu2009=u20095), and linear IgA disease (nu2009=u20091) were included. Treatment with 500u2009mg RTX (nu2009=u20096) or 1,000u2009mg RTX (nu2009=u200922) was administered on days 1 and 15. Eight patients received additional 500u2009mg RTX at months 6 and 12. Overall, DC was achieved in 67.9%, PR in 57.1%, and CR in 21.4% of the cases. During follow-up, 66.7% patients relapsed. Repeated treatment with RTX led to remission (PR or CR) in 85.7% of the retreated cases. No significant difference in response between pemphigoid subtypes was found. IgA-dominant cases (nu2009=u20095) achieved less DC (20 vs. 81.3%; pu2009=u20090.007), less PR (20 vs. 62.5%; pu2009=u20090.149), and less CR (0 vs. 18.8%; pu2009=u20090.549) compared to IgG-dominant cases (nu2009=u200916). Five severe adverse events and three deaths were reported. One death was possibly related to RTX and one death was disease related. Conclusion RTX can be effective in recalcitrant IgG-dominant pemphigoid diseases, however not in those where IgA is dominant.

Determining the Incidence of Pneumocystis Pneumonia in Patients With Autoimmune Blistering Diseases Not Receiving Routine Prophylaxis

Importance Pneumocystis pneumonia (PCP) is a potentially lethal opportunistic infection that primary prophylaxis can help prevent. The risk of prophylactic therapy must be weighed against the incidence of PCP in the patient population. Prophylaxis most frequently involves trimethoprim-sulfamethoxazole, with second-line therapies, including atovaquone, dapsone, and pentamide. The indication for prophylaxis in immunocompromised patients without HIV is less well defined. Previously, an incidence of at least 3.5% has been proposed as a cutoff to justify prophylaxis. Objective To assess the incidence of PCP in patients with autoimmune blistering diseases receiving no routine prophylaxis. Design, Setting, and Participants This was a retrospective analysis of patient medical records to determine the incidence of PCP infections. The multicenter study was performed at tertiary care centers that provide care for patients with autoimmune blistering disease in Germany, Italy, Singapore, Israel, and the Netherlands. Patients had a confirmed diagnosis of pemphigus vulgaris/foliaceus, bullous pemphigoid, epidermolysis bullosa acquisita, mucous membrane pemphigoid/cicatricial pemphigoid, or anti-p200 pemphigoid. Main Outcomes and Measures To determine the incidence of PCP defined as patients with the International Classification of Diseases, Ninth Revision (ICD-9), code 136.3, for PCP, or free text documentation of PCP occurring based on characteristic radiographic findings with elevated lactate dehydrogenase, or hospitalization for pneumonia with bronchioalveolar lavage demonstrating Pneumocystis jiroveci on confirmatory stains. Results A total of 801 patients with autoimmune blistering diseases were included in this study; their mean (SD) age was 66.5 (17.6) years, and a total of 465 (58%) were female. Only 1 patient developed PCP, resulting in an incidence rate of 0.1%. This incidence significantly fell below the recommended threshold of 3.5% (0.1% vs 3.5%, &khgr;21u2009=u200927.0; Pu2009<u2009.001). This incidence was significantly lower than the previously reported incidence of PCP in all immunosuppressed dermatologic patients (0.1% vs 1.3%; &khgr;21u2009=u20098.2; Pu2009=u2009.004). Conclusions and Relevance Routine Pneumocystis prophylaxis for patients with autoimmune blistering diseases does not seem to be warranted. Patients with autoimmune blistering disease seem to have a lower risk of PCP than the general population of immunosuppressed dermatology patients. Risks of routine prophylaxis include hyperkalemia, hypoglycemia, photosensitivity, thrombocytopenia, and more rare adverse reactions.